NDLI: BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells

Content Provider	PubMed Central
Author	Ramirez, Pablo Rettig, Michael P. Uy, Geoffrey L. Elena, Deych Holt, Matthew S. Ritchey, Julie K. Dipersio, John F.
Abstract	Here we show that interruption of the VCAM-1/VLA-4 axis with a small molecule inhibitor of VLA-4, BIO5192, results in a 30-fold increase in mobilization of murine hematopoietic stem and progenitors (HSPCs) over basal levels. An additive affect on HSPC mobilization (3-fold) was observed when plerixafor (AMD3100), a small molecule inhibitor of the CXCR-4/SDF-1 axis, was combined with BIO5192. Furthermore, the combination of granulocyte colony-stimulating factor (G-CSF), BIO5192, and plerixafor enhanced mobilization by 17-fold compared with G-CSF alone. HSPCs mobilized by BIO5192 or the combination of BIO5192 and plerixafor mobilized long-term repopulating cells, which successfully engraft and expand in a multilineage fashion in secondary transplantation recipients. Splenectomy resulted in a dramatic enhancement of G-CSF–induced mobilization while decreasing both plerixafor- and BIO5192-induced mobilization of HSPCs. These data provide evidence for the utility of small molecule inhibitors of VLA-4 either alone or in combination with G-CSF or AMD3100 for mobilization of hematopoietic stem and progenitor cells.
Related Links	http://dx.doi.org/10.1182/blood-2008-10-184721
Ending Page	1343
Page Count	4
Starting Page	1340
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	7
Volume Number	114
Language	English
Publisher	American Society of Hematology
Publisher Date	2009-08-13
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells